Cholesterol gallstone disease (CGD) is one of the most prevalent digestive diseases, leading to considerable financial and social burden worldwide. Ursodeoxycholic acid (UDCA) is the only bile acid drug approved by FDA for the non-surgical treatment of gallstones. However, a molecular link between UDCA and CGD is unclear. Data suggest that farnesoid X receptor (FXR), a bile acid nuclear receptor, could protect against the development of CGD. Thus, the identification of selective and potent modulators for FXR with enhanced efficacy is of crucial and significant value. Provided herein are solutions to these and other problems in the art.